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Valentina Sukonina¹, Haixia Ma¹, Wei Zhang¹

¹Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

|February 1, 2019

概括

叉头转录因子FOXK1和FOXK2通过上调关键酶和抑制线粒体的酸盐氧化来激活有氧糖解. 这种新陈代谢重编程对于细胞适应和能量提取至关重要.

科学领域:

细胞代谢
分子生物学
生物化学

背景情况:

细胞适应环境变化和提取能量对于生存至关重要.
虽然一般的代谢途径已被理解,但营养利用适应的确切机制仍然不清楚.
叉头转录因子 (FOXK1和FOXK2) 参与细胞对禁食和饥饿的反应.

研究的目的:

阐明FOXK1和FOXK2在调节细胞代谢中的机制作用.
研究这些转录因子如何影响糖解和线粒体氧化之间的平衡.
了解FOXK1和FOXK2对有氧糖解的影响.

主要方法:

使用细胞培养物的体外研究.
在动物模型中的体内实验.
对原始人类细胞的分析.
测试以测量与糖解和线粒体代谢相关的酶活性和基因表达.

主要成果:

通过上调诸如基酶-2,酸果基酶,酸盐基酶和乳酸脱酶等酶来诱导FOXK1和FOXK2.
这些因素通过增加pyruvate脱酶激酶 (PDK1,PDK4) 和降低pyruvate脱酶酸酶1 (PDP1) 来抑制线粒体的pyruvate氧化.
这导致酸化和抑制酸盐脱酶复合体的增加,有利于乳酸盐生产而不是线粒体呼吸.

结论:

FOXK1 和 FOXK2 作为重编程细胞代谢向有氧糖解的关键调节剂.
抑制FOXK1和FOXK2可以逆转这种代谢表型.
这些发现突显了FOXK1/FOXK2在代谢适应中的关键作用,并提供了对有氧糖解的机制见解.

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